Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEPicolinafenCat.No.:HY-W711035CASNo.:137641-05-5Synonyms:AC900001分子式:C??H??F?N?O?分子量:376.3作用靶點(diǎn):p38MAPK;PI3K;CalciumChannel;ReactiveOxygenSpecies(ROS);Apoptosis;CytochromeP450作用通路:MAPK/ERKPathway;PI3K/Akt/mTOR;MembraneTransporter/IonChannel;NeuronalSignaling;Immunology/Inflammation;MetabolicEnzyme/Protease;NF-κB;Apoptosis儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性 Picolinafen是一種八氫番茄紅素去飽和酶(PDS)抑制型吡啶類除草劑。Picolinafen可控制闊葉雜草的生長并且干擾類胡蘿卜素生物合成。Picolinafen對(duì)豬胚胎滋養(yǎng)外胚層細(xì)胞(pTr)和子宮腔上皮細(xì)胞(pLE)具有細(xì)胞毒性。Picolinafen可通過誘導(dǎo)ROS積累、鈣耗竭，激活MAPK和PI3K信號(hào)通路，導(dǎo)致細(xì)胞活力下降、凋亡(apoptosis)增加、遷移能力受損以及著床相關(guān)基因表達(dá)改變。Picolinafen可影響pTr和pTr著床能力。Picolinafen對(duì)哺乳動(dòng)物的LD50值為2.7mg/kg，對(duì)魚類為7μg/L。Picolinafen在斑馬魚胚胎發(fā)育過程中表現(xiàn)出毒性效應(yīng)[1][2]。體外研究Picolinafen(0.2-6μM,48h)decreasescellviabilityandalterscellcycleprogressioninpTrandpLEcells[1].Picolinafen(1-4μM,48h)inducesapoptosis,impairsself-assemblyofcellspheroidsandinterfereswithmitochondrialintegrityandcalciumhomeostasisinpTrandpLEcells[1].Picolinafen(1-4μM,2-48h)causesROSaccumulationanddisruptsintracellularCa2+regulationinpTrandpLEcells[1].Picolinafen(4μM,15-24h)inhibitspTrcellmigrationandaltersthetranscriptionalregulationofgenesinvolvedinapoptosisandimplantation[1].Picolinafen(1-4μM,3h)activatestheMAPKandPI3K/AKTsignalingpathwaysinpTrandpLEcells[1].CellCycleAnalysis[1]CellLine:pTrandpLEcells1/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEConcentration:1,2,4μMIncubationTime:48hResult:IncreasedG1phaseinpLEcells.DecreasedbothG1andSphasesinpTrcells.ReducedtheratioofcellsintheG2/Mphasebyapproximately0.65-and0.6-foldinpTrandpLEcells,respectively.IncreasedtheratioofcellsintheG1phasebyapproximately5.68-and4.03-foldinpTrandpLEcells,respectively.CellViabilityAssay[1]CellLine:pTrandpLEcellsConcentration:0.2,0.5,1,2,4,5,6μMIncubationTime:48hResult:DecreasedtheviabilityofpTrcells(IC50=4.33μM)andpLEcells(IC50=5.54μM).ApoptosisAnalysis[1]CellLine:pTrandpLEcellsConcentration:1,2,4μMIncubationTime:48hResult:Increasedearlyapoptosisby3.23and1.5foldinpTrandpLEcells,respectively.Increasedlateapoptosisby3.1and1.73foldinpTrandpLEcells,respectively.CellMigrationAssay[1]CellLine:pTrcellsConcentration:4μMIncubationTime:15hResult:DecreasedthepercentageofwoundclosureinpTrcellsby0.31fold.RealTimeqPCR[1]CellLine:pTrandpLEcellsConcentration:4μMIncubationTime:24h2/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEResult:IncreasedBAXby1.31fold,BAK1by1.3fold,andCASP3by1.4foldinpTrcells.IncreasedBAXby1.72fold,BAK1by1.34foldinpLEcells.IncreasedtheexpressionlevelofthecytochromeP450enzyme-codinggeneCYP1A1inpTrcells.ReducedtheexpressionofFOLR1andITGAV,whichareinvolvedinimplantationinpTrcells.WesternBlotAnalysis[1]CellLine:pTrandpLEcellsConcentration:1,2,4μMIncubationTime:3hResult:IncreasedtheabundanceofphosphorylatedERK1/2,JNK,andp38andtheexpressionlevelsofPI3K/AKTinpTrcells.IncreasedtheabundanceofphosphorylatedJNKandp38inpLEcells.Suppressedp-ERK1/2levelsbyU0126(HY-12031A)andAdezmapimod(SB203580)(HY-10256)treatmentsinpTrandpLEcells.Reducedp-JNKbySP600125(HY-12041),Wortmannin(HY-10197)andU0126inpTrandpLEcells.Restoredthelevelsofp-p38andSP203580,whereasSP600125increasedthephosphorylationofp38inpLEcells.Down-regulatedphospho-AKTlevelsfollowingtreatmentwithWortmanninandSB203580,whereasonlyWortmannininhibitedp-AKTinpLEcells.Inhibitedthephosphorylationofp70S6KbyWortmannin,U0126,andSB203580inbothcelllines.InhibitedS6bywortmanninandU0126inpTrcells,whereasthistargetwassignificantlydown-regulatedbyallfourinhibitorsinpLEcells.體內(nèi)研究Picolinafen(0.1-100μM,incubation,0-5days)exhibitsanLC50of10μMat3daysand5μMat5daysinzebrafishembryos[2].Picolinafen(1-10μM,incubation,24-72h)exhibitstoxiceffectsduringzebrafishembryogenesis[2].AnimalModel:Zebrafishembryo[2]Dosage:1,5,10μMAdministration:Incubationfor24,48and72hResult:Causedembryohatchingat48h,with“deadhatchedembryos”observedandreduced“l(fā)iveembryos”to30%,withonly22%survivingself-hatchingat10μMat72h.Impairedearlyembryogenesisevidencedbythelargereyesandbrain,thesmalleryolk3/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEsacandheartandatailcurvaturereductionfrom180°to89°at10μM.Increasedtheapoptoticcellslocalizedintheeyesandtailregionofzebrafishembryo.DestroyedDNAandinducedcelldeathespeciallyintheeyesandyolk-sacofzebrafishembryos.Reducedoxidativestressduringembryogenesisat5μM.Decreasedtheamountofangiogenesisinthetrunkofzebrafishembryosat5μM.REFERENCESParkW,etal.ROSaccumulationandcalciumdepletion,leadingtoapoptosisinporcineembryonictrophectodermanduterineluminalepithelialcellsduringtheperi-implantationperiod.Theriogenology.2023Apr15;201:12-23.LeeJY,etal.Picolinafenexertsdevelopmentaltoxicityviathesuppressionofoxidativestressandangiogenesisi